1. Mitochondrial movement is impaired in neuronal cell bodies expressing mutant MFN2 proteins.
Mitochondrial movement is impaired in neuronal cell bodies expressing mutant MFN2 proteins. DRG neurons were infected with lentiviruses encoding wild-type or disease mutant MFN2 constructs, together with a mitochondrially targeted DsRed2 (DsRm) and photoactivatible GFP (PAGFPm). PAGFP is a variant of GFP and has minimal fluorescence at baseline, but its fluorescence increases ∼100-fold when photoactivated with 405 or 413 nm light (Patterson and Lippincott-Schwartz, 2002). After 10 d in culture, mitochondria in approximately half of the cell body were photoactivated using the 405 nm laser (yellow box indicates region of photoexcitation), and individual cells were reimaged 36 h later. Neurons expressing wild-type MFN2 (WT) showed an even redistribution of photoactivated mitochondria throughout the cell body after 36 h. Neurons expressing mutant MFN2 proteins had clustered, fragmented mitochondria. After 36 h, there was very little movement of mitochondria from the region of photoexcitation. The decrement in the post-photoactivation signal suggests that some mitochondrial fusion still took place, although because of the marked mobility defect, this cannot be measured as an independent variable.
Robert H. Baloh et al. J. Neurosci. 2007;27:
©2007 by Society for Neuroscience